A randomized, double-blind, placebo-controlled study has been conducted, and intralesional interferon alfa-2b was tested in the treatment of genital warts. This study design was to give 1 million units interferon alfa-2b intralesionally into the base of each of five external genital warts per patient, on a Monday-Wednesday-Friday treatment schedule for 3 weeks (total of nine injections). Forty-two patients were entered (20 randomized to receive interferon and 22 placebo injections). There were 43.8% of patients on the interferon treatment arm of the double-blind portion of the study who had complete disappearance of all warts, with an additional 25% of patients showing greater than 50% shrinkage of visible warts. On the placebo arm 14.3% showed a complete response, with an additional 14.3% showing greater than 50% shrinkage. This difference between interferon and placebo treatment was statistically significant (p less than 0.03). We conclude that intralesional interferon alfa-2b has significant activity in the treatment of genital warts.